Mutations in the plasma glycoprotein Factor VIII (FVIII) have been implicated as the causative agent of hemophilia Type A. FVIII (Mw 243) circulates predominantly as a hetero-dimeric protein consisting of a Ca (II) linked light chain (LC) and heavy chain (HC). The latter contains A1-A2-B domains (Mw 163) and the LC contains the A3-C1-C2 domains (Mw 80). We are interested in measuring the thermodynamic parameters associated with FVIII and its subunits to determine the domain stability and domain-domain interactions in FVIII. By combining the calorimetric data obtained for the parent compound and individual components (i.e., HC, LC, and FVIII with/without EDTA), we hope to characterize how domain-domain interactions contribute to the overall structural stability of FVIII.